The nature of 1,4-benzodiazepines/receptor interactions

A general survey of receptor binding affinity data for 1,4-benzodiazepines, associated with the results of crystal structure determinations, quantum-mechanical calculations, structure-activity relationships and pharmacokinetic data, leads the authors to propose a new scheme for benzodiazepine-receptor interactions. 1,4-Benzodiazepines would interact with positively charged receptor sites by means of two hydrogen bonds accepted respectively by the carbonyl oxygen at position 2 and by the N4 atom of the diazepine ring. A third point of interaction would be given by the phenyl ring at C5 which would fit almost exactly in a hydrophobic pocket of the receptor.